Graft-Versus-Host DiseasePhase 1NCT01633229
Bone Marrow Stromal Cell Infusions for Stem Cell Transplant Complications
A Phase 1 study testing Bone Marrow Stromal Cell Infusion in people with Graft-Versus-Host Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Bone marrow stromal cells (BMSC) from bone marrow biopsies can be used to treat disorders that cause inflammation and immune system diseases. BMSC have been used to treat graft versus host disease (GVHD), a complication that can develop after stem cell transplants. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graft-Versus-Host Disease
- What is being tested?
- Bone Marrow Stromal Cell Infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Nov 2011to 8 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 5.1.1 History of allogeneic SCT
- Any subject who has received an allogeneic SCT at NIH is eligible if they have one or more of the following conditions. Subjects may continue to receive standard treatments for their condition but may not be entered onto a new investigational protocol to treat the condition during the period of evaluation of BMSC infusions.
- 5.1.1.1 Acute GVHD
- Biopsy confirmed within 14 days of investigational intervention (unless not possible to perform because of anatomical location or clinical contraindication) acute GVHD affecting gut and/or liver and/or skin, defined as steroid refractory: failure to respond to greater than or equal to 2mg/kg methylprednisolone (or equivalent) after 7 days OR steroid dependent: requiring methylprednisolone (or equivalent) greater than or equal to 1mg/kg for greater than or equal to 7days for control of GVHD. GVHD affecting the skin alone is rarely lethal and is excluded. Acute GVHD is defined using the NIH consensus definition inclusive of Classic acute (< 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features) AND Persistent/recurrent/late onset acute (> 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features).
- 5.1.1.2 Marrow Failure
- Poor graft function in the presence of >95% donor myeloid chimerism: defined as platelet or red cell transfusion dependent OR absolute neutrophil count persisting <500/ (Micro)l for 14 days without other reversible or treatable causes.
Show all 18Show fewer
- 5.1.1.3 Pulmonary injury
- Lung injury from: Diffuse alveolar hemorrhage (DAH), Cryptogenic Organizing Pneumonia (COP), Bronchiolitis Obliterans Syndrome (BOS), idiopathic interstitial pneumonia (IP), Adult respiratory distress syndrome (ARDS) diagnosed by exclusion of active infection. Also worsening pneumomediastinum or pneumothorax persisting after 7 days; at risk for causing hemodynamic changes in association with any of these diagnoses.
- 5.1.1.4 Hepatic injury
- Clinically diagnosed sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease (VOD), with bilirubin > 2 times ULN or transaminases >3 times ULN and rising.
- 5.1.1.5 Hemorrhagic cystitis (HC)
- HC requiring continuous bladder irrigation OR requiring red cell or platelet transfusions at least intermittently for the past 7 days OR HC unresponsive to antivirals after 10 days.
- 5.1.1.6 Gastrointestinal tract
- Pneumoperitoneum, bowel perforation not susceptible to corrective surgery OR blood transfusion requirement > 1 unit per day for 7 days.
- 5.1.2 Age: greater than or equal to 18 years of age and less than or equal to 75 years of age.
- 5.1.3 Birth Control
- Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
- 5.1.4 Transplant performed at NIH.
Who cannot join
- 5.2.1 Breast feeding or pregnant females (due to unknown risk to fetus or newborn).
- 5.2.2 Allergic to gentamicin
- 5.2.3 Weight less than 20 kg (not informative for research sampling)
- 5.2.4 Patients with significant organ failure at baseline as evidenced by any of the following:
- <TAB>Symptomatic cardiac failure at rest or with minimal activity or exertion for which intervention is indicated
- <TAB>Creatinine > 3.0 X ULN
- <TAB>Decreased oxygen saturation at rest (e.g. pulse oximeter < 88% or PaO2 less than or equal to 55 mmHg)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Study of Bone Marrow Stromal Cell Infusions to Treat Acute Graft Versus Host Disease, Marrow Failure and Tissue Injury After Allogeneic Stem Cell Transplantation
Background:
- Bone marrow stromal cells (BMSC) from bone marrow biopsies can be used to treat disorders that cause inflammation and immune system diseases. BMSC have been used to treat graft versus host disease (GVHD), a complication that can develop after stem cell transplants. BMSC have also been used to treat other post-transplant complications, like marrow failure or tissue injury.
- The National Institutes of Health (NIH) has developed a procedure for collecting and preserving BMSC from volunteer donors. These donors have passed tests to ensure that their cells are healthy enough to be used for treatment. Researchers want to use the collected cells to treat people with GVHD, marrow failure, or tissue injury following stem cell transplants.
Read more
Objectives:
- To test the safety and effectiveness of NIH-collected BMSC to treat complications from stem cell transplants.
Eligibility:
- Individuals between 18 and 75 years of age who have complications from stem cell transplants.
- Complications are acute GVHD, poor bone marrow function, or tissue or organ damage.
Design:
- Participants will be screened with a physical exam and medical history. They will also have imaging studies and blood tests.
- Participants will provide blood, skin, and bone marrow samples before the BMSC treatment. Additional samples, including tissue samples, will be collected after the start of treatment.
- Participants will have up to three BMSC infusions. There will be a week between each infusion. Participants will be monitored closely during each infusion. Any side effects will be treated.
- Treatment will be monitored with frequent blood tests and physical exams.
- After the end of the infusions, participants will have regular followup visits for up to 2 years.
Read the detailed description
Bone marrow stromal cells (BMSC) derived from bone marrow aspiration/biopsy have important anti-inflammatory and immunosuppressive properties that make them suitable candidates for cellular therapy of inflammatory and degenerative disorders. BMSC suppress lymphocyte immune responsiveness and can hone in to sites of inflammation and promote healing. BMSC were first used in man to successfully treat refractory acute graft versus host disease (aGVHD). A recent multicenter study treating refractory aGVHD reported a 66% response rate and a sustained survival in responding patients. BMSC are currently being evaluated in acute GVHD in several ongoing studies worldwide. BMSC have also been used to treat post-transplant conditions not directly due to GVHD. Responses have been reported in hemorrhagic cystitis, and pneumoperitoneum. BMSC are also under evaluation in the treatment of inflammatory and autoimmune disorders.
The Cell Processing Section of the Department of Transfusion Medicine at the Clinical Center NIH has developed a procedure for collecting, expanding and cryopreserving clinical grade BMSC under an FDA Drug Master File (DMF). Marrow will be aspirated from volunteer donors participating on protocol 10-CC-0053 who have passed the standard screening for blood and marrow donors and BMSC will be expanded in vitro. Since it is not necessary to HLA-match BMSC donors with their recipient for this study, a BMSC repository will be used as the source of BMSC for this study.
This will be the first trial of the safety of the NIH BMSC cellular product in stem cell transplant recipients. In this phase I study, open to adult NIH allogeneic stem cell transplantation (SCT) recipients, we will evaluate the safety of a fixed dose of BMSC infusions (target dose of 2 x 106 BMSCs /kg (+/- 10%)) in patients with acute GVHD, marrow failure or tissue injury following allogeneic SCT. Up to three BMSC infusions will be given every 7 3 days apart. Safety will be monitored continuously with a stopping rule for toxicity based on the treatment-related serious adverse event rate. Organ-specific clinical responses will be measured. Where possible we will also attempt to identify transfused BMSC in sites of damage in biopsy material. It is planned to accrue up to 10 subjects over a 6-month period.
- Conditions
- Graft-Versus-Host Disease
- Being tested
- Bone Marrow Stromal Cell Infusion
- Keywords
- Immune Suppression, BMSC, GVHD, Marrow Failure, Regimen Related Toxicity, Graft-Versus-Host Disease
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bone Marrow Stromal Cell InfusionProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint to this study is to characterize the safety of bone marrow stromal cells (BMSC).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2012 (estimated)
- Study start14 Nov 2011
- Primary completion1 Jul 2013
- Study completion8 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Graft-Versus-Host DiseaseStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Minocher M Battiwalla, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01633229
- Sponsor's protocol ID
- 120010
- Other IDs
- 12-H-0010
- Status last verified
- 8 Mar 2018
- First submitted
- 30 Jun 2012
- Last updated
- 12 Dec 2019
- Results posted
- No
Publications
Ogawa M, LaRue AC, Drake CJ. Hematopoietic origin of fibroblasts/myofibroblasts: Its pathophysiologic implications. Blood. 2006 Nov 1;108(9):2893-6. doi: 10.1182/blood-2006-04-016600. Epub 2006 Jul 13.
PubMed 16840726Bhanu NV, Trice TA, Lee YT, Gantt NM, Oneal P, Schwartz JD, Noel P, Miller JL. A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells. Blood. 2005 Jan 1;105(1):387-93. doi: 10.1182/blood-2004-04-1599. Epub 2004 Sep 14.
PubMed 15367428Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004 Jul 7;292(1):81-5. doi: 10.1001/jama.292.1.81.
PubMed 15238594
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Bone Marrow Stromal Cell Infusions to Treat Acute Graft Versus Host Disease, Marrow Failure and Tissue Injury After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01633229
- Acronym / sponsor ID
- 120010
- Conditions
- Graft-Versus-Host Disease
- Keywords
- Immune Suppression, BMSC, GVHD, Marrow Failure, Regimen Related Toxicity, Graft-Versus-Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 14 Nov 2011
- Primary completion
- 1 Jul 2013 (actual)
- Study completion
- 8 Mar 2018 (actual)
- First posted
- 4 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Bone marrow stromal cells (BMSC) from bone marrow biopsies can be used to treat disorders that cause inflammation and immune system diseases. BMSC have been used to treat graft versus host disease (GVHD), a complication that can develop after stem cell transplants. BMSC have also been used to treat other post-transplant complications, like marrow failure or tissue injury.
- The National Institutes of Health (NIH) has developed a procedure for collecting and preserving BMSC from volunteer donors. These donors have passed tests to ensure that their cells are healthy enough to be used for treatment. Researchers want to use the collected cells to treat people with GVHD, marrow failure, or tissue injury following stem cell transplants.
Objectives:
- To test the safety and effectiveness of NIH-collected BMSC to treat complications from stem cell transplants.
Eligibility:
- Individuals between 18 and 75 years of age who have complications from stem cell transplants.
- Complications are acute GVHD, poor bone marrow function, or tissue or organ damage.
Design:
- Participants will be screened with a physical exam and medical history. They will also have imaging studies and blood tests.
- Participants will provide blood, skin, and bone marrow samples before the BMSC treatment. Additional samples, including tissue samples, will be collected after the start of treatment.
- Participants will have up to three BMSC infusions. There will be a week between each infusion. Participants will be monitored closely during each infusion. Any side effects will be treated.
- Treatment will be monitored with frequent blood tests and physical exams.
- After the end of the infusions, participants will have regular followup visits for up to 2 years.
Detailed description
Bone marrow stromal cells (BMSC) derived from bone marrow aspiration/biopsy have important anti-inflammatory and immunosuppressive properties that make them suitable candidates for cellular therapy of inflammatory and degenerative disorders. BMSC suppress lymphocyte immune responsiveness and can hone in to sites of inflammation and promote healing. BMSC were first used in man to successfully treat refractory acute graft versus host disease (aGVHD). A recent multicenter study treating refractory aGVHD reported a 66% response rate and a sustained survival in responding patients. BMSC are currently being evaluated in acute GVHD in several ongoing studies worldwide. BMSC have also been used to treat post-transplant conditions not directly due to GVHD. Responses have been reported in hemorrhagic cystitis, and pneumoperitoneum. BMSC are also under evaluation in the treatment of inflammatory and autoimmune disorders.
The Cell Processing Section of the Department of Transfusion Medicine at the Clinical Center NIH has developed a procedure for collecting, expanding and cryopreserving clinical grade BMSC under an FDA Drug Master File (DMF). Marrow will be aspirated from volunteer donors participating on protocol 10-CC-0053 who have passed the standard screening for blood and marrow donors and BMSC will be expanded in vitro. Since it is not necessary to HLA-match BMSC donors with their recipient for this study, a BMSC repository will be used as the source of BMSC for this study.
This will be the first trial of the safety of the NIH BMSC cellular product in stem cell transplant recipients. In this phase I study, open to adult NIH allogeneic stem cell transplantation (SCT) recipients, we will evaluate the safety of a fixed dose of BMSC infusions (target dose of 2 x 106 BMSCs /kg (+/- 10%)) in patients with acute GVHD, marrow failure or tissue injury following allogeneic SCT. Up to three BMSC infusions will be given every 7 3 days apart. Safety will be monitored continuously with a stopping rule for toxicity based on the treatment-related serious adverse event rate. Organ-specific clinical responses will be measured. Where possible we will also attempt to identify transfused BMSC in sites of damage in biopsy material. It is planned to accrue up to 10 subjects over a 6-month period.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 5.1.1 History of allogeneic SCT
- Any subject who has received an allogeneic SCT at NIH is eligible if they have one or more of the following conditions. Subjects may continue to receive standard treatments for their condition but may not be entered onto a new investigational protocol to treat the condition during the period of evaluation of BMSC infusions.
- 5.1.1.1 Acute GVHD
- Biopsy confirmed within 14 days of investigational intervention (unless not possible to perform because of anatomical location or clinical contraindication) acute GVHD affecting gut and/or liver and/or skin, defined as steroid refractory: failure to respond to greater than or equal to 2mg/kg methylprednisolone (or equivalent) after 7 days OR steroid dependent: requiring methylprednisolone (or equivalent) greater than or equal to 1mg/kg for greater than or equal to 7days for control of GVHD. GVHD affecting the skin alone is rarely lethal and is excluded. Acute GVHD is defined using the NIH consensus definition inclusive of Classic acute (< 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features) AND Persistent/recurrent/late onset acute (> 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features).
- 5.1.1.2 Marrow Failure
Key exclusion criteria (7 listed)
- 5.2.1 Breast feeding or pregnant females (due to unknown risk to fetus or newborn).
- 5.2.2 Allergic to gentamicin
- 5.2.3 Weight less than 20 kg (not informative for research sampling)
- 5.2.4 Patients with significant organ failure at baseline as evidenced by any of the following:
- <TAB>Symptomatic cardiac failure at rest or with minimal activity or exertion for which intervention is indicated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bone Marrow Stromal Cell Infusion | Procedure or surgery | – |
Primary outcome
The primary endpoint to this study is to characterize the safety of bone marrow stromal cells (BMSC).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
- Background: PubMed 16840726Ogawa M, LaRue AC, Drake CJ. Hematopoietic origin of fibroblasts/myofibroblasts: Its pathophysiologic implications. Blood. 2006 Nov 1;108(9):2893-6. doi: 10.1182/blood-2006-04-016600. Epub 2006 Jul 13.
- Background: PubMed 15367428Bhanu NV, Trice TA, Lee YT, Gantt NM, Oneal P, Schwartz JD, Noel P, Miller JL. A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells. Blood. 2005 Jan 1;105(1):387-93. doi: 10.1182/blood-2004-04-1599. Epub 2004 Sep 14.
- Background: PubMed 15238594Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004 Jul 7;292(1):81-5. doi: 10.1001/jama.292.1.81.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Minocher M Battiwalla, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bone Marrow Stromal Cell Infusion in people with Graft-Versus-Host Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint to this study is to characterize the safety of bone marrow stromal cells (BMSC).. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01633229, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2019.